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Publication : hPCL3s Promotes Hepatocellular Carcinoma Metastasis by Activating β-Catenin Signaling.

First Author  Cai Z Year  2018
Journal  Cancer Res Volume  78
Issue  10 Pages  2536-2549
PubMed ID  29483096 Mgi Jnum  J:262294
Mgi Id  MGI:6158992 Doi  10.1158/0008-5472.CAN-17-0028
Citation  Cai Z, et al. (2018) hPCL3s Promotes Hepatocellular Carcinoma Metastasis by Activating beta-Catenin Signaling. Cancer Res 78(10):2536-2549
abstractText  Two isoforms of human Polycomb-like protein 3 (hPCL3) have been reported as components of the nuclear Polycomb repressive complex 2 (PRC2), with the short isoform (hPCL3s) showing a dominant cytoplasmic localization. The function of cytoplasmic hPCL3s has, however, not been addressed. In this study, we report that hPCL3s is upregulated in clinical hepatocellular carcinoma (HCC) samples and its expression correlated with HCC clinical features. hPCL3s positively regulated the migration, invasion, and metastasis of HCC cells. hPCL3s interacted with components of the cytoplasmic beta-catenin destruction complex, inhibited beta-catenin degradation, and activated beta-catenin/T-cell factor signaling. Downstream of the beta-catenin cascade, IL6 mediated the motility-promoting functions of hPCL3s. Forced expression of hPCL3s in the liver of a HCC mouse model promoted tumorigenesis and metastasis. Taken together, these data show that hPCL3s promotes the metastasis of HCC by activating the beta-catenin/IL6 pathway.Significance: hPCL3s has an oncogenic role in hepatocellular carcinoma by activating the beta-catenin/IL6 signaling axis to promote metastasis. Cancer Res; 78(10); 2536-49. (c)2018 AACR.
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